Process for the preparation of phenoxybenzamine

Abstract

The present invention provides a process for the preparation of N-phenoxyisopropyl ethanolamine of Formula (II) and its conversion to Phenoxybenzamine of Formula (I) or pharmaceutically acceptable salts thereof.

We claim: 
     
       1. A process for the preparation of N-phenoxyisopropyl ethanolamine of Formula (II) or salt thereof; 
       
         
           
           
               
               
           
         
         which comprises reacting a compound of Formula (III a ); 
       
       
         
           
           
               
               
           
         
         wherein R is C 1-12  straight or branched-chain alkyl, C 2-12  cyclo alkyl, C 6-12  aryl and each hydrogen in R is optionally substituted with one or more halogen or C 1-6  straight or branched-chain alkyl; 
         with mono ethanolamine to obtain N-phenoxyisopropyl ethanolamine of Formula (II). 
       
     
     
       2. A process for the preparation of Phenoxybenzamine of Formula (I) or pharmaceutically acceptable salts thereof: 
       
         
           
           
               
               
           
         
         which comprises: 
         a. further reacting the compound of Formula (II) or salt thereof prepared as claimed in  claim 1 , with benzyl chloride to obtain N-(phenoxyisopropyl)-N-benzylethanolamine of Formula (I-A) or salt thereof; 
       
       
         
           
           
               
               
           
         
         b. reacting the compound of Formula (I-A) or salt thereof with a chlorinating agent to obtain Phenoxybenzamine of Formula (I) or pharmaceutically acceptable salt thereof. 
       
     
     
       3. The process as claimed in  claim 2 , wherein the chlorinating agent used in step (b) is selected from thionyl chloride, phosphorus pentachloride, phosphoryl chloride, phosgene, oxalyl chloride or triphenylphosphine dichloride.